来自以色列金蝎毒液的钾通道毒素对兔血管中对克罗卡林反应的影响。

Effects of potassium channel toxins from Leiurus quinquestriatus hebraeus venom on responses to cromakalim in rabbit blood vessels.

Strong P N, Weir S W, Beech D J, Hiestand P, Kocher H P

Jerry Lewis Muscle Research Centre, Department of Paediatrics and Neonatal Medicine, Royal Postgraduate Medical School, London.

Br J Pharmacol. 1989 Nov;98(3):817-26. doi: 10.1111/j.1476-5381.1989.tb14610.x.

Abstract

The effects of fractionated Leiurus quinquestriatus hebraeus venom on cromakalim-induced 86Rb+ efflux in rabbit aortic smooth muscle were examined. 2. Crude venom (0.1-30 micrograms ml-1) produced a concentration-dependent decrease of 1 microM cromakalim-induced 86Rb+ response. The maximum blocking activity attainable was approximately 60%. 3. Fractionation of crude venom by gel permeation chromatography and subsequent chromatography on a cation ion-exchange column, produced two fractions (X and XI), active in the 86Rb+ blocking assay. 4. Fraction XII contained charybdotoxin (approximately 85% pure). After a final high performance liquid chromatography (h.p.l.c.) purification step, the purified toxin failed to inhibit the cromakalim-stimulated 86Rb+ efflux although it was a potent inhibitor of A23187-induced K+ flux in human erythrocytes and the large conductance calcium-activated potassium channel in rabbit portal vein smooth muscle. 5. Subsequent purification of fraction X by h.p.l.c. yielded a minor peak which contained 86Rb+ blocking activity. This subfraction was also capable of inhibiting apamin-sensitive, angiotensin II-stimulated K+ flux in guinea-pig hepatocytes. 6. It is concluded that the potassium channel opened by cromakalim in rabbit aortic smooth muscle is not blocked by charybdotoxin but by another distinct toxin in the venom of Leiurus quinquestriatus hebraeus.

摘要

研究了分步给予以色列金蝎毒液对兔主动脉平滑肌中克罗卡林诱导的⁸⁶Rb⁺外流的影响。2. 粗毒液（0.1 - 30微克/毫升）使1微摩尔克罗卡林诱导的⁸⁶Rb⁺反应呈浓度依赖性降低。可达到的最大阻断活性约为60%。3. 通过凝胶渗透色谱法对粗毒液进行分级分离，随后在阳离子交换柱上进行色谱分离，得到两个在⁸⁶Rb⁺阻断试验中有活性的级分（X和XI）。4. 级分XII含有蝎毒素（纯度约为85%）。经过最后一步高效液相色谱（h.p.l.c.）纯化后，纯化后的毒素未能抑制克罗卡林刺激的⁸⁶Rb⁺外流，尽管它是A23187诱导的人红细胞钾外流以及兔门静脉平滑肌中大电导钙激活钾通道的有效抑制剂。5. 随后通过h.p.l.c.对级分X进行纯化，得到一个含有⁸⁶Rb⁺阻断活性的小峰。该亚级分也能够抑制豚鼠肝细胞中对蜂毒明肽敏感的、血管紧张素II刺激的钾外流。6. 得出的结论是，克罗卡林在兔主动脉平滑肌中打开的钾通道不受蝎毒素阻断，而是受以色列金蝎毒液中的另一种不同毒素阻断。